Orthopedics

Allograft Alternatives: Bone Substitutes and Beyond

Stuart B. Goodman, MD, PhD

  • Orthopedics. 2010;33(9)
  • Posted September 1, 2010

Abstract

Excessive wear debris, deep infection, periprosthetic fracture, and other causes can lead to bone loss associated with total joint replacements. When performing revisions, surgeons are often preoccupied by the failed implant and the method of replacement, and neglect an opportunity to replenish lost bone. Thus, when formulating a plan for revision total joint replacement, the surgeon should consider not only the hardware that should be used, but also ways in which lost bone could be restored. Autograft bone provides the best source for osteoprogenitor cells, growth factors, and a scaffold. However, autograft is limited in supply, and is generally associated with another incision, dissection, and accompanying morbidity. Osteoconductive bone void fillers such as morselized cancellous allograft bone, polymeric scaffolds, and biodegradable ceramics each have their merits and deficiencies; however, all of these materials function as a scaffold only, without the ability to induce bone formation. Osteoinductive growth factors are essential to bone growth and remodeling; however, exogenous growth factors are expensive, are given in large nonphysiological doses, may yield unpredictable clinical results, and may have significant adverse effects. Demineralized bone matrix contains a scaffold and variable amounts of several growth factors. Recently, the use of mesenchymal stem cells and osteoprogenitors, together with a suitable scaffold carrier has gained increasing popularity. With the addition of appropriate growth factors, this combination can provide all the necessary components for osteogenesis. Future basic and clinical research will define the indications and outcomes for new combination products for reconstruction of lost bone associated with revision total joint replacement.

Bone loss in total joint replacement is a significant issue, and can be due to periprosthetic osteolysis associated with wear debris, infection, fracture, and other causes. In the elderly, bone loss associated with revision surgery is often accomplished using artificial materials; however in younger patients, reconstitution of bone serves as a foundation for future revision procedures.

Bone is a composite material that is approximately 70% inorganic (calcium compounds) and 30% organic, of which Type I collagen is the main component. This forms the scaffold on which cells reside. Osteoblasts and their precursors, osteoclasts, fat cells, and cells of the hematopoietic cell lineage make up the majority of cells within long bones, along with a complex vascular network. The final components are the proteins that regulate bone formation, resorption and remodeling, which continues throughout life.

The gold standard for replenishing lost bone is autograft, which contains a scaffold, osteoblasts, and the necessary signaling proteins and molecules. However, autograft is in short supply, may be insufficient due to poor quality (eg, osteoporosis) and may be associated with complications at the graft site. Thus alternatives to autograft bone have emerged. In order to use these alternative treatments in a scientific manner, one must understand specific concepts and processes regarding bone formation, resorption, and remodeling.1-3

Osteoconductive materials are scaffolds that provide the appropriate framework for bone to grow in sites where bone naturally occurs. Examples include allograft, hydroxyapatite and tricalcium phosphate. Osteoinductive factors or materials have the capacity to induce bone formation when placed in a site where normally no bone forms. Demineralized bone matrix and bone morphogenic proteins (BMPs) are examples of osteoinductive materials. Osteopromotive grafts have the ability to enhance natural bone formation by stimulatory signals. By themselves, they do not have the capacity to induce new bone formation at nonskeletal sites. An example of an osteopromotive material is platelet rich plasma. Finally, osteogenic materials contain all the necessary elements to make bone directly, including osteoblasts or their precursors, a scaffold, and growth factors and signaling molecules.

Bone substitutes are used frequently to replenish lost bone stock during revision…

Abstract

Excessive wear debris, deep infection, periprosthetic fracture, and other causes can lead to bone loss associated with total joint replacements. When performing revisions, surgeons are often preoccupied by the failed implant and the method of replacement, and neglect an opportunity to replenish lost bone. Thus, when formulating a plan for revision total joint replacement, the surgeon should consider not only the hardware that should be used, but also ways in which lost bone could be restored. Autograft bone provides the best source for osteoprogenitor cells, growth factors, and a scaffold. However, autograft is limited in supply, and is generally associated with another incision, dissection, and accompanying morbidity. Osteoconductive bone void fillers such as morselized cancellous allograft bone, polymeric scaffolds, and biodegradable ceramics each have their merits and deficiencies; however, all of these materials function as a scaffold only, without the ability to induce bone formation. Osteoinductive growth factors are essential to bone growth and remodeling; however, exogenous growth factors are expensive, are given in large nonphysiological doses, may yield unpredictable clinical results, and may have significant adverse effects. Demineralized bone matrix contains a scaffold and variable amounts of several growth factors. Recently, the use of mesenchymal stem cells and osteoprogenitors, together with a suitable scaffold carrier has gained increasing popularity. With the addition of appropriate growth factors, this combination can provide all the necessary components for osteogenesis. Future basic and clinical research will define the indications and outcomes for new combination products for reconstruction of lost bone associated with revision total joint replacement.

Bone loss in total joint replacement is a significant issue, and can be due to periprosthetic osteolysis associated with wear debris, infection, fracture, and other causes. In the elderly, bone loss associated with revision surgery is often accomplished using artificial materials; however in younger patients, reconstitution of bone serves as a foundation for future revision procedures.

Bone is a composite material that is approximately 70% inorganic (calcium compounds) and 30% organic, of which Type I collagen is the main component. This forms the scaffold on which cells reside. Osteoblasts and their precursors, osteoclasts, fat cells, and cells of the hematopoietic cell lineage make up the majority of cells within long bones, along with a complex vascular network. The final components are the proteins that regulate bone formation, resorption and remodeling, which continues throughout life.

The gold standard for replenishing lost bone is autograft, which contains a scaffold, osteoblasts, and the necessary signaling proteins and molecules. However, autograft is in short supply, may be insufficient due to poor quality (eg, osteoporosis) and may be associated with complications at the graft site. Thus alternatives to autograft bone have emerged. In order to use these alternative treatments in a scientific manner, one must understand specific concepts and processes regarding bone formation, resorption, and remodeling.1-3

Osteoconductive materials are scaffolds that provide the appropriate framework for bone to grow in sites where bone naturally occurs. Examples include allograft, hydroxyapatite and tricalcium phosphate. Osteoinductive factors or materials have the capacity to induce bone formation when placed in a site where normally no bone forms. Demineralized bone matrix and bone morphogenic proteins (BMPs) are examples of osteoinductive materials. Osteopromotive grafts have the ability to enhance natural bone formation by stimulatory signals. By themselves, they do not have the capacity to induce new bone formation at nonskeletal sites. An example of an osteopromotive material is platelet rich plasma. Finally, osteogenic materials contain all the necessary elements to make bone directly, including osteoblasts or their precursors, a scaffold, and growth factors and signaling molecules.

Bone substitutes are used frequently to replenish lost bone stock during revision total joint replacement.1-3 Perhaps the most common bone substitute is morselized cancellous allograft bone chips, which are osteoconductive only, and rely on a viable vascularized bone bed for incorporation. Demineralized bone matrix (DBM) is derived when explanted bone is subjected to strong acids to extract the mineral phase. This process leaves behind the growth factors, the noncollagenous proteins and collagen, and therefore DBM is osteoconductive and osteoinductive.

Different DBMs have different degrees of osteoinductivity, as shown by in vitro and in vivo preclinical experiments.1-4 However, few prospective, randomized clinical studies delineate the efficacy of DBM, and the material can be costly. Porous ceramics function as a scaffold and bone void filler, and are osteoconductive, facilitating the ingrowth of cells. These materials can be sterilized and are moldable, but generally do not have sufficient mechanical properties to support full immediate weight bearing.

Recombinant growth factors such as BMP-2 and BMP-7 (OP-1) have osteoinductive capacity. Growth factors bind to membrane receptors on the surface of bone cells and progenitors, thereby leading to the proliferation, differentiation, and maturation of these cells, and neighboring cells (a paracrine effect). Growth factors are powerful in small amounts, but are expensive. Their use is primarily restricted to spine surgery and complex tibial fractures. Surgeons should appreciate the indications and contraindications for use of these substances.

Cell-based therapies have recently emerged as a new alternative. Most products combine harvested, enriched bone cells, and their precursors from the patient’s own bone marrow with a suitable carrier, thus forming an osteogenic graft. This option is becoming more popular, especially when cellular elements are needed due to compromise of the bone bed associated with poor vascularity, previous infection, irradiation, etc. This has also been a viable treatment for cases of osteonecrosis.

When dealing with bone defects in cases of joint replacement and osteonecrosis, consideration should be given to general patient characteristics, the defect size and location, and the local biological and mechanical environment. Appropriate bone graft materials and substances should be chosen according to a rational understanding of the above principles.

References

  1. Laurencin CT, ed. Bone Graft Substitutes. West Conshohocken, PA: ASTM; 2003.
  2. Friedlander G, Mankin HJ, Goldberg VM, eds. Bone Grafts and Bone Graft Substitutes. Rosemont, IL; American Academy of Orthopaedic Surgeons; 2006.
  3. Greenwald AS, Boden SD, Goldberg VM, Khan Y, Laurencin CT, Rosier RN; American Academy of Orthopaedic Surgeons. Bone-graft substitutes: facts, fictions and application. The Committee on Biological Implants. J Bone Joint Surg Am. 2001; 83(Suppl 2 Pt 2):98-103.
  4. Peterson B, Whang PG, Iglesias R, Wang JC, Lieberman JR. Osteoconductivity of commercially available demineralized bone matrix. J Bone Joint Surg Am. 2004; 86(10):2243-2250.

Author

Dr Goodman is from the Department of Orthopedic Surgery, Stanford University School of Medicine, Stanford, California.

Dr Goodman has no relevant financial relationships to disclose.

Presented at Current Concepts in Joint Replacement 2009 Winter Meeting; December 9-12, 2009; Orlando, Florida.

Correspondence should be addressed to: Stuart B. Goodman, MD, PhD, Stanford University Medical Center Outpatient Center, 450 Broadway St, M/C 6342, Redwood City, CA 94063 (goodbone@stanford.edu).

doi: 10.3928/01477447-20100722-31

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